3-Methylene cephalosporanic acid esters are described as a by product in the conversion of penicillin sulfoxides to cephalosporins by Morin et al. in U.S. Pat. No. 3,275,626.
Additional methods for preparing acylated 3-methylene cephalosporin esters and their conversion to the corresponding 3-methyl compounds are disclosed by Chauvette in U.S. Pat. No. 3,932,393 and in J. Org. Chem., Vol. 38, p. 2994-2999. Chauvette in U.S. Pat. Nos. 3,925,372 and 3,962,227 describes converting the 3-methylene cephalosporins to the corresponding 3-hydroxy compound which can then be converted to a 3-halo cephalosporin.
Ponticello et al. in U.S. Pat. No. 3,883,518 describe the preparation of various acylated 3-methylene cephalosporins including those having a 7.alpha.-methoxy substituent. Ponticello et al. describe reacting the methylene compound with a source of halogen to yield an acylated 3-halo-3-halomethyl cephalosporin which is treated with base to yield the acylated 3-halomethyl compound.
Others methods of preparing acylated 3-methylene cephalosporins and their conversion to acylated 3-methyl cephalosporins are described by Ochiai et al. in U.S. Pat. Nos. 3,792,995 and 3,929,775 and in J.C.S. Chem. Comm., 1972, p. 800-801, Tetrahedron Letters, Vol. 23, p. 2341, J.C.S. Perkin I, 1974, p. 258-262, and Tetrahedron, Vol. 31, p. 115-122.
Various acylated 7.alpha.-methoxy and desmethoxy cephalosporins having a heterothiomethyl group in the 3-position are disclosed as possessing useful antibacterial activity as note U.S. Pat. Nos. 3,516,997, 3,641,021, 3,759,904, 3,821,207, 3,855,213, 3,867,380, 3,920,639, 3,978,051, 3,989,697, etc.